We asked whether specifications of different regions of the rodent and avian telencephalon during development involved the acquisition of differential adhesive properties. Cells from different regions were aggregated in a short-term aggregation assay, and their segregation was analyzed. Both neurons and precursor cells from cortex segregate from striatal cells at early, but not later, stages, whereas cells from rodent neocortex and hippocampus segregated only during later stages. Segregation was abolished when Ca2+-dependent but not Ca2+-independent adhesion molecules were selectively removed. Thus, selective adhesion appears to be a conserved mechanism that restricts cellular mixing and might serve to maintain positional information during forebrain development. A candidate for mediating the Ca2+-dependent segregation is the CD15 (Lewis(x)) carbohydrate epitope, which is selectively expressed by mammalian cortex but not striatum.